Exploring long-term cancer survivors' care experiences and unmet needs: protocol for a qualitative study.

BACKGROUND: The number of cancer survivors has increased in recent decades, and the majority of them suffer from sequelae of their disease and treatment. This study, which is part of the larger research project OPTILATER, aims to explore different aspects of care services for long-term survivors (≥ 5 years after initial cancer diagnosis) in Germany. The study places an emphasis on the situation of people from different age groups, with different socio-demographic and cultural backgrounds, and sexually and gender diverse individuals. METHODS: To investigate experiences related to follow-up care, focus groups (n = 2) will be conducted with members of patient advisory councils and advocacy groups, representatives of communities, healthcare workers and networks, as well as members of Associations of Statutory Health Insurance Physicians. Guided interviews will be carried out with patients and relatives (n = 40) to investigate needs, barriers and obstacles in terms of follow-up care. On this basis, additional focus groups (n = 2) will be carried out to derive possible scenarios for improving the consideration of needs. Focus groups and interviews will follow a semi-structured format and will be analysed content-analytically. Focus groups and interviews will be conducted online, recorded, transcribed, and analysed independently by two persons. DISCUSSION: The qualitative approach is considered suitable because of the exploratory research aims. The identification of experiences and barriers can reveal disparities and optimization potential in the care of long-term cancer survivors.

Job satisfaction of advanced practice nurses in cancer care: A systematic review.

PURPOSE: To identify, evaluate, and summarise evidence about advanced practice nurses' (APNs') job satisfaction in cancer care and its related factors. METHODS: A systematic review was performed including a narrative synthesis. Relevant evidence was identified from searches of three databases: Medline (PubMed), EBSCO (CINAHL), and PsychInfo. This systematic review searched for relevant articles published in English between 2000 and 2020. A structured process according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement was followed. The articles critical appraisal was based on the Mixed-Methods Appraisal Tool. Narrative data synthesis was based on the extracted data (study characteristics, type of questionnaire, level of job satisfaction, related factors, and risk of bias). RESULTS: Just four articles met the inclusion criteria and were included in the systematic review. Job satisfaction of APNs providing cancer care in different care settings varied from low to high. Satisfying factors were personal, role, work, and institutional factors, whereas dissatisfies included the work setting and stress factors. Different measurement tools of the job satisfaction level were used, which might lead to non-comparable results. CONCLUSION: The number of included studies and the findings from this systematic review present underinvestigated content according to the influence of patient group demands on APNs' job satisfaction. Evidence of patient group-specific factors relevant to APNs' job satisfaction could not be found. Further research is needed to address the influence of advanced nursing practice and patient group-related factors on job satisfaction.

Radiomics Study of Thyroid Ultrasound for Predicting BRAF Mutation in Papillary Thyroid Carcinoma: Preliminary Results.

BACKGROUND AND PURPOSE: It is not known how radiomics using ultrasound images contribute to the detection of BRAF mutation. This study aimed to evaluate whether a radiomics study of gray-scale ultrasound can predict the presence or absence of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation in papillary thyroid cancer. MATERIALS AND METHODS: The study retrospectively included 96 thyroid nodules that were surgically confirmed papillary thyroid cancers between January 2012 and June 2013. BRAF mutation was positive in 48 nodules and negative in 48 nodules. For analysis, ROIs from the nodules were demarcated manually on both longitudinal and transverse sonographic images. We extracted a total of 86 radiomics features derived from histogram parameters, gray-level co-occurrence matrix, intensity size zone matrix, and shape features. These features were used to build 3 different classifier models, including logistic regression, support vector machine, and random forest using 5-fold cross-validation. The performance including accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve, of the different models was evaluated. RESULTS: The incidence of high-suspicion nodules diagnosed on ultrasound was higher in the BRAF mutation-positive group than in the mutation-negative group (P = .004). The radiomics approach demonstrated that all classification models showed moderate performance for predicting the presence of BRAF mutation in papillary thyroid cancers with an area under the curve value of 0.651, accuracy of 64.3%, sensitivity of 66.8%, and specificity of 61.8%, on average, for the 3 models. CONCLUSIONS: Radiomics study using thyroid sonography is limited in predicting the BRAF mutation status of papillary thyroid carcinoma. Further studies will be needed to validate our results using various diagnostic methods.

[Anesthesiological concepts in fast-track arthroplasty]. / Anästhesiologische Konzepte in der Fast-Track-Endoprothetik.

Whereas only a few years ago the only expectation of skilful anesthesia was an undisturbed execution of surgical procedures, today this has changed to a perioperative responsibility in which all physicians involved in the treatment process try to optimize the existing circumstances and risks of the patient before, during and after surgery. Thus, the tasks for the anesthesiologist have been mainly extended to a rapid recovery strategy with as few side effects as possible, such as nausea and vomiting or postoperative cognitive deficits (POCD). The establishment of evident structures and the introduction of suitable perioperative procedures with the goal of maintaining homeostasis, adequate opioid-sparing pain treatment and rapid postoperative convalescence determine the anesthesiological fast-track concept.

[Preoperative management and patient education in fast-track arthroplasty]. / Präoperatives Management und Patientenschulung in der Fast-Track-Endoprothetik.

BACKGROUND: Patient management and education are essential for successful fast-track hip/knee arthroplasty. Individual risk stratification as well as educational seminars play an important role in optimizing preoperative risk factors. OBJECTIVES: Preoperative risk factors are discussed, and optimization strategies are highlighted in the context of the current literature. Further, our own results of an interdisciplinary patient seminar and a patient information app shall be discussed. MATERIALS AND METHODS: In addition to the authors' own strategy concerning preoperative patient management and the execution of the patient information seminar and app, the essential papers from the literature will be discussed. RESULTS: Preoperative risk factors (diabetes, obesity, anaemia, etc.) bear the danger of a prolonged length-of-stay with increased morbidity and mortality. Preoperative optimization can reduce the risk of complications and minimize the failure of the fast-track pathway. Educational seminars and patient information apps may reduce anxiety and postoperative analgesic consumption. CONCLUSION: A good preoperative patient management in fast-track arthroplasty can reduce the risk of complications and a prolonged length-of-stay. A comprehensive patient education with educational seminars and an app contributes to optimally preparing the patient for surgery.

Surgical solutions for refractory J-pouch inlet obstruction.

AIM: Many surgeons consider total proctectomy with ileal pouch-anal anastomosis as the treatment of choice for patients with medically refractory ulcerative colitis or ulcerative colitis with dysplasia. However, obstruction occurring at the pouch inlet or involving the afferent limb can be refractory to nonoperative or endoscopic management. Historically, these refractory obstructions have usually required resection of the pouch. There is now increasing evidence to suggest that pouch salvage surgery may be feasible in these patients. METHODS: A retrospective review was performed of all patients of a single surgical practice who underwent a neo ileal-pouch anastomosis for J-pouch inlet obstructions between 2000 and 2017. Data collected included patient demographics, preoperative workup, intra-operative findings, type of surgical intervention and postoperative outcomes. RESULTS: Surgical interventions were performed on eight patients with J-pouch inlet obstructions. Six patients had inlet strictures or acute angulations at the inlet, which were either bypassed or resected and primarily anastomosed. Two patients had internal hernias posterior to the mesentery, with volvulus of the pouch. At a mean follow-up of 36.5 months, all patients retained their pouches and the mean number of daily bowel movements was eight. Two major and two minor complications occurred. DISCUSSION: J-pouch inlet obstructions may take years to develop. In patients with obstruction who are refractory to endoscopic or medical treatment, good functional results may be obtained with pouch salvage procedures. With increasing numbers of J-pouches being performed, awareness of novel surgical techniques is important.

Exploring the efficacy and cellular uptake of sorafenib in colon cancer cells by Raman micro-spectroscopy.

In recent years, many subcellular proteins have emerged as promising therapeutic targets in oncology. One crucial target is the epidermal growth factor receptor. Inhibition of this receptor has significantly improved the survival rate of patients for many cancers. However, oncogenic mutations such as B-RAFV600E have rendered tumours resistant to this therapeutic approach. Therefore, this mutation has emerged as a potential target for cancer therapy. Sorafenib is developed to overcome the B-RAFV600E mutation and restore the response of the mutated tumour to therapy. Here, we explore the efficacy and distribution of sorafenib at a cellular level using colon cancer cell lines with B-RAFV600E or K-RASG12V mutations. The Raman results detected significant sorafenib-induced spectral differences in both cell lines. In addition, the western blot and real-time cell analysis in vitro assays revealed that the ERK phosphorylation and the cellular proliferation of cells are inhibited, respectively, in the sorafenib-treated cells. Thus, the observed Raman spectral changes illustrate the potent effect of sorafenib on cells despite the presence of the B-RAFV600E or K-RASG12V mutations. These results are in agreement with the clinical studies, where patients with the B-RAFV600E mutation respond to sorafenib. Furthermore, the Raman spectral imaging results have shown the uptake and the distribution of sorafenib in colon cancer cells with the B-RAFV600E mutation through its label-free marker bands in the fingerprint region. The present results of sorafenib efficacy and distribution in cells demonstrate the potential of Raman micro-spectroscopy as the in vitro assay for the assessment of drugs, which is important in drug discovery.

Extracardiac intrapericardial myxosarcoma causing right ventricular outflow tract obstruction in a dog.

A 13-year-old male castrated pomeranian cross was referred for evaluation of episodes of collapse and a suspected cardiac mass. The presence of a mass at the base of the heart within the pericardial space was confirmed by echocardiography. Additional diagnostics included computed tomography, ultrasound-guided fine-needle aspirate, and thoracic radiographs. The mass was surgically debulked and diagnosed as myxosarcoma via histopathology. This case report describes the diagnostic imaging, laboratory findings, and short-term positive clinical outcome of a dog with a myxosarcoma in a previously undescribed location.

Histogram analysis of greyscale sonograms to differentiate between the subtypes of follicular variant of papillary thyroid cancer.

AIM: To evaluate the diagnostic value of histogram analysis using ultrasound (US) to differentiate between the subtypes of follicular variant of papillary thyroid carcinoma (FVPTC). MATERIALS AND METHODS: The present study included 151 patients with surgically confirmed FVPTC diagnosed between January 2014 and May 2016. Their preoperative US features were reviewed retrospectively. Histogram parameters (mean, maximum, minimum, range, root mean square, skewness, kurtosis, energy, entropy, and correlation) were obtained for each nodule. RESULTS: The 152 nodules in 151 patients comprised 48 non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs; 31.6%), 60 invasive encapsulated FVPTCs (EFVPTCs; 39.5%), and 44 infiltrative FVPTCs (28.9%). The US features differed significantly between the subtypes of FVPTC. Discrimination was achieved between NIFTPs and infiltrative FVPTC, and between invasive EFVPTC and infiltrative FVPTC using histogram parameters; however, the parameters were not significantly different between NIFTP and invasive EFVPTC. CONCLUSION: It is feasible to use greyscale histogram analysis to differentiate between NIFTP and infiltrative FVPTC, but not between NIFTP and invasive EFVPTC. Histograms can be used as a supplementary tool to differentiate the subtypes of FVPTC.

Innovative substance 2250 as a highly promising anti-neoplastic agent in malignant pancreatic carcinoma - in vitro and in vivo.

BACKGROUND: Former studies already revealed the anti-neoplastic properties of the anti-infective agent Taurolidine (TRD) against many tumor species in vitro and in vivo. Its anti-proliferative and cell death inducing capacity is largely due to its main derivative Taurultam (TRLT). In this study it could be demonstrated, that substance 2250 - a newly defined innovative structural analogue of TRLT - exhibits an anti-neoplastic effect on malignant pancreatic carcinoma in vitro and in vivo. METHODS: The anti-neoplastic potential of substance 2250 as well as its mode of action was demonstrated in extensive in vitro analysis, followed by successful and effective in vivo testings, using xenograft models derived from established pancreatic cancer cell lines as well as patient derived tissue. RESULTS: Our functional analysis regarding the role of oxidative stress (ROS) and caspase activated apoptosis showed, that ROS driven programmed cell death (PCD) is the major mechanisms induced by substance 2250 in pancreatic carcinoma. What is strongly relevant towards clinical practice is especially the observed inhibition of patient derived pancreatic cancer tumor growth in mice treated with this new substance in combination with its sharply higher metabolic stability. CONCLUSION: These encouraging results provide new therapeutical opportunities in pancreatic cancer treatment and build the basis for further functional analysis as well as first clinical studies for this promising agent.

What Is the Ideal Core Number for Ultrasonography-Guided Thyroid Biopsy of Cytologically Inconclusive Nodules?

BACKGROUND AND PURPOSE: Core needle biopsy of the thyroid under ultrasonographic guidance provides a larger tissue sample and may facilitate a more precise histologic diagnosis, reducing the need for repetitive fine-needle aspiration or a diagnostic operation. However, there is no consensus regarding the ideal number of specimens to be obtained for ultrasonography-guided core needle biopsy. The aim of this study was to decide the ideal core number for ultrasonography-guided core needle biopsy of cytologically inconclusive nodules. MATERIALS AND METHODS: Sixty consecutive biopsies were performed in 60 thyroid nodules with Bethesda Category I or III cytology. Three biopsy cores were obtained for each thyroid nodule. The first biopsy specimens were taken from the nodule, while the second and third specimens obtained included the nodular tissue, nodular capsule, and surrounding parenchyma. Diagnostic ability was evaluated according to the following: protocol A, first specimen; protocol B, first and second specimens; and protocol C, all specimens. The McNemar test was used for statistical analysis. RESULTS: Of the 60 nodules, diagnostic ability was achieved in 41 nodules (68%) with protocol A, in 56 nodules (93%) with protocol B, and in 58 nodules (97%) with protocol C. The diagnostic ability of protocols B and C was significantly higher than that of protocol A (all P values < .001). However, the diagnostic ability of protocol B was not significantly different from that of protocol C. CONCLUSIONS: Ultrasonography-guided core needle biopsy for cytologically inconclusive thyroid nodules should obtain at least 2 core specimens with intranodular and capsule targets.

Optimizing structural and mechanical properties of cryogel scaffolds for use in prostate cancer cell culturing.

Prostate cancer (PCa) currently is the second most diagnosed cancer in men and the second most cause of cancer death after lung cancer in Western societies. This sets the necessity of modelling prostatic disorders to optimize a therapy against them. The conventional approach to investigating prostatic diseases is based on two-dimensional (2D) cell culturing. This method, however, does not provide a three-dimensional (3D) environment, therefore impeding a satisfying simulation of the prostate gland in which the PCa cells proliferate. Cryogel scaffolds represent a valid alternative to 2D culturing systems for studying the normal and pathological behavior of the prostate cells thanks to their 3D pore architecture that reflects more closely the physiological environment in which PCa cells develop. In this work the 3D morphology of three potential scaffolds for PCa cell culturing was investigated by means of synchrotron X-ray computed micro tomography (SXCµT) fitting the according requirements of high spatial resolution, 3D imaging capability and low dose requirements very well. In combination with mechanical tests, the results allowed identifying an optimal cryogel architecture, meeting the needs for a well-suited scaffold to be used for 3D PCa cell culture applications. The selected cryogel was then used for culturing prostatic lymph node metastasis (LNCaP) cells and subsequently, the presence of multi-cellular tumor spheroids inside the matrix was demonstrated again by using SXCµT.

Is there a role for salvage radiotherapy in locally advanced breast cancer refractory to neoadjuvant chemotherapy?

INTRODUCTION: Locally advanced breast cancer (LABC) is a major problem, especially in developing countries. The standard treatment for LABC is neoadjuvant chemotherapy, with or without anti-Her2 therapy, followed by surgery, radiotherapy, and adjuvant systemic treatment if appropriate. However, there are few data in the literature addressing alternatives when neoadjuvant chemotherapy fails to reduce the tumour for surgery. MATERIALS AND METHODS: We conducted a retrospective study including all patients who had non-metastatic LABC treated with neoadjuvant chemotherapy and who were not eligible for surgical resection; these patients were submitted to salvage radiotherapy (RTX) between January 2000 and December 2012 at the Brazilian National Cancer Institute. RESULTS: Fifty-seven patients were included, with a median age of 51 (23-72) years. The most frequent clinical stages were IIIA and IIIB, corresponding to 19.3% and 70.2%, respectively; mean tumour size was 8.74 (3-18) cm, and 44 patients (77.2%) had nodal involvement. Chemotherapeutic regimens containing anthracyclines were prescribed to 98.2% of the patients. Fifteen patients (26.3%) received taxanes and anthracyclines. Radiation dose was 50 Gy divided into 25 fractions; 43 patients (75.4%) had their tumours downsized by RTX and underwent mastectomy. Overall survival (OS) was 38 (23-52) months. Patients who were submitted to surgery had an OS of 49 (28-70) months and those who were not eligible for mastectomy after radiotherapy had an OS of 18 (9-27) months. CONCLUSION: This retrospective study confirms that RTX is an effective treatment to downsize LABC tumours with low or no response to chemotherapy, thereby enabling surgical resection which may improve overall patient outcome.

Screening of gestational diabetes mellitus in early pregnancy by oral glucose tolerance test and glycosylated fibronectin: study protocol for an international, prospective, multicentre cohort trial.

INTRODUCTION: As the accurate diagnosis and treatment of gestational diabetes mellitus (GDM) is of increasing importance; new diagnostic approaches for the assessment of GDM in early pregnancy were recently suggested. We evaluate the diagnostic power of an 'early' oral glucose tolerance test (OGTT) 75 g and glycosylated fibronectin (glyFn) for GDM screening in a normal cohort. METHODS AND ANALYSIS: In a prospective cohort study, 748 singleton pregnancies are recruited in 6 centres in Switzerland, Austria and Germany. Women are screened for pre-existing diabetes mellitus and GDM by an 'early' OGTT 75 g and/or the new biomarker, glyFn, at 12-15 weeks of gestation. Different screening strategies are compared to evaluate the impact on detection of GDM by an OGTT 75 g at 24-28 weeks of gestation as recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). A new screening algorithm is created by using multivariable risk estimation based on 'early' OGTT 75 g and/or glyFn results, incorporating maternal risk factors. Recruitment began in May 2014. ETHICS AND DISSEMINATION: This study received ethical approval from the ethics committees in Basel, Zurich, Vienna, Salzburg and Freiburg. It was registered under http://www.ClinicalTrials.gov (NCT02035059) on 12 January 2014. Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02035059.

A randomized, double-blind, phase III, multicentre study to evaluate the safety and efficacy of BF-200 ALA (Ameluz(®) ) vs. placebo in the field-directed treatment of mild-to-moderate actinic keratosis with photodynamic therapy (PDT) when using the BF-RhodoLED(®) lamp.

BACKGROUND: Multiple actinic keratosis (AK) lesions may arise from the cancerization of large, sun-damaged skin areas. Although photodynamic therapy (PDT) is considered the most effective therapeutic option, the efficacy and safety of field treatment of multiple AK lesions with PDT has never before been tested in a pivotal trial. OBJECTIVES: To evaluate the efficacy, safety and cosmetic outcome of BF-200 ALA (a nanoemulsion formulation containing 10% aminolaevulinic acid hydrochloride) combined with the BF-RhodoLED(®) lamp for the field-directed treatment of mild-to-moderate AK with PDT. METHODS: The study was performed as a randomized, multicentre, double-blind, placebo-controlled, parallel-group, phase III trial with BF-200 ALA and placebo in seven centres in Germany. A total of 94 patients were enrolled in this study; 87 were randomized (55 patients received BF-200 ALA, 32 received placebo). Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Illumination was performed with the PDT lamp BF-RhodoLED (635 nm ± 9 nm) until a total light dose of 37 J cm(-2) was achieved. RESULTS: BF-200 ALA was superior to placebo with respect to patient complete clearance rate (91% vs. 22%, P < 0·0001) and lesion complete clearance rate (94·3% vs. 32·9%, P < 0·0001) after a maximum of two PDTs. The confirmatory analysis of all key secondary variables supported this superiority" should not be skipped since this is an important result. Treatment-emergent adverse events (TEAEs) were experienced by 100% of the BF-200 ALA group and 69% of the placebo group. The most commonly reported TEAEs were TEAEs of the application site. The cosmetic outcome was improved in the BF-200 ALA group compared with placebo. CONCLUSIONS: Field-directed therapy with BF-200 ALA and BF-RhodoLED lamp is highly effective and well tolerated for multiple mild-to-moderate AK lesions, providing greatly improved skin quality.

Modified Core Biopsy Technique to Increase Diagnostic Yields for Well-Circumscribed Indeterminate Thyroid Nodules: A Retrospective Analysis.

BACKGROUND AND PURPOSE: The results of conventional core biopsy for some thyroid nodules with indeterminate cytology have still remained indeterminate. The aim of this study was to evaluate whether the ultrasonography-guided core needle biopsy technique containing the nodule, capsular portion, and surrounding parenchyma was more effective than a conventional method in enhancing diagnostic yield for circumscribed solid thyroid nodules without malignant sonographic features. MATERIALS AND METHODS: This retrospective comparative study evaluated 26 thyroid nodules in 26 consecutive patients between 2006 and 2010. They were biopsied by using a conventional method, and 61 nodules from 60 patients were biopsied by using a modified ultrasonography-guided core needle biopsy technique in 2013. The patients enrolled in this study presented with circumscribed solid thyroid nodules without malignant sonographic features, classified as nondiagnostic or atypia/follicular lesions of undetermined significance at previous cytology. The ultrasonography-guided core needle biopsy results of the 2 groups were compared. RESULTS: The rate of inconclusive ultrasonography-guided core needle biopsy results was 34.6% (9/26) in the conventional group and 11.4% (7/61) in the modified technique group (P = .018). There was no significant difference in the mean size of the nodules between the 2 groups (P = .134). The malignancy rate was 33% (3/9) for the conventional group and 52% (27/52) for the modified technique group (P = .473). The most common malignant pathology was a follicular variant of papillary thyroid carcinoma and follicular adenoma was the most common benign lesion. CONCLUSIONS: For circumscribed solid nodules without malignant sonographic features with indeterminate cytology, the ultrasonography-guided core needle biopsy technique containing the nodule, capsular portion, and surrounding parenchyma is more effective in diagnostic yield compared with a conventional method that biopsies the intranodular portion.

Proton pencil beam scanning for mediastinal lymphoma: the impact of interplay between target motion and beam scanning.

The purpose of this study was to assess the feasibility of proton pencil beam scanning (PBS) for the treatment of mediastinal lymphoma. A group of 7 patients of varying tumor size (100-800 cc) were planned using a PBS anterior field. We investigated 17 fractions of 1.8 Gy(RBE) to deliver 30.6 Gy(RBE) to the internal target volume (ITV). Spots with σ ranging from 4 mm to 8 mm were used for all patients, while larger spots (σ = 6-16 mm) were employed for patients with motion perpendicular to the beam (⩾5 mm), based on initial 4-dimensional computed tomography (4D CT) motion evaluation. We considered volumetric repainting such that the same field would be delivered twice in each fraction. The ratio of extreme inhalation amplitude and regular tidal inhalation amplitude (free-breathing variability) was quantified as an indicator of potential irregular breathing during the scanning. Four-dimensional dose was calculated on the 4D CT scans based on the respiratory trace and beam delivery sequence, implemented by partitioning the spots into separate plans on each 4D CT phase. Four starting phases (end of inhalation, end of exhalation, middle of inhalation and middle of exhalation) were sampled for each painting and 4 energy switching times (0.5 s, 1 s, 3 s and 5 s) were tested, which resulted in 896 dose distributions for the analyzed cohort. Plan robustness was measured for the target and critical structures in terms of the percent difference between 'delivered' dose (4D-evaluated) and planned dose (calculated on average CT). It was found that none of the patients exhibited highly variable or chaotic breathing patterns. For all patients, the ITV D98% was degraded by <2% (standard deviations âˆ¼ 0.1%) when averaged over the whole treatment course. For six out of seven patients, the average degradation of ITV D98% per fraction was within 5% . For one patient with motion perpendicular to the beam (⩾5 mm), the degradation of ITV D98% per fraction was up to 15%, which was mitigated to 2% by employing larger spots and repainting. Deviation of mean lung dose was at most 0.2 Gy(RBE) (less than 1% of prescribed dose, 30.6 Gy(RBE)), while the deviation of heart maximum dose and cord maximum dose could exceed 5% of the prescribed dose. No significant difference in either target coverage or normal tissue dose was observed for different energy switching times compared via two-sided Wilcoxon signed-rank tests (p < 0.05). This feasibility study demonstrates that, for mediastinal lymphoma, the impact of the interplay effect on the PBS plan robustness is minimal when volumetric repainting and/or larger spots are employed.

Activated MHC-mismatched T helper-1 lymphocyte infusion enhances GvL with limited GvHD.

DLI is traditionally used to provide graft-versus-leukemia (GvL) effects when given to patients relapsing post-hematopoietic cell transplantation (HCT). However, it is often associated with significant GvHD and has only modest efficacy against acute leukemias. Therefore, novel cellular therapies are needed to improve the outcome of high-risk or relapsed leukemia patients following HCT. Activated T helper-1 (aTh-1) lymphocytes are CD4(+)CD25(+)CD40L(+)CD62L(lo) effector memory cells that produce large amounts of IFN-γ and TNF-α. We demonstrate that post-transplant adoptive aTh-1 cell therapy enhances GvL with limited GvHD in an MHC-mismatched murine BMT model. aTh-1 infusions result in superior leukemia-free survival when compared with unstimulated splenocytes (SC), purified CD4(+) T-cells and T-cell-enriched SC. aTh-1 cells display cytotoxicity against A20 leukemia cells in vitro and persist in vivo for at least 2 months following adoptive transfer. Furthermore, in contrast to unstimulated SC, aTh-1 cell infusion is associated with only transient, mild suppression of donor-derived hematopoiesis. aTh-1 cell therapy is safe, effective and warrants further investigation as an alternative to DLI.

Differences in the HbA1c-lowering efficacy of glucagon-like peptide-1 analogues between Asians and non-Asians: a systematic review and meta-analysis.

AIMS: To compare the HbA1c-lowering efficacy of glucagon-like peptide-1 (GLP-1) analogues between Asians and non-Asians with type 2 diabetes. METHODS: We searched randomized controlled trials from MEDLINE, EMBASE, LILACS, CENTRAL and ClinicalTrials.gov. Studies described in English were included if the treatment duration was 12 weeks or more, information about ethnicity and baseline HbA1c values were available and a GLP-1 analogue was compared with a placebo. For the ethnic comparison, we divided the studies into Asian-dominant studies (≥ 50% Asian participants) and non-Asian-dominant studies (<50% Asian participants). RESULTS: Among the 837 searched studies, 15 trials were included for the meta-analysis. The weighted mean difference of HbA1c with GLP-1 analogues was -1.16% [95% confidence interval (CI) -1.48, -0.85] in the Asian-dominant studies and -0.83% (95% CI -0.97, -0.70) in the non-Asian-dominant studies. The between-group difference was -0.32% (95% CI -0.64, -0.01; p = 0.04). The relative risk (RR) with 95% CIs for achieving the target HbA1c ≤ 7.0% tended to be greater in the Asian-dominant studies [RR 5.7 (3.8, 8.7)] than in the non-Asian-dominant studies [RR 2.8 (2.4, 3.3)]. Body weight changes were similar between the two groups. Hypoglycaemia tended to be more common in Asian-dominant studies (RR 2.8 [2.3, 3.5]) than in non-Asian-dominant studies (RR 1.5 [1.2, 1.8]), but severe hypoglycaemia was very rare in both groups. CONCLUSION: GLP-1 analogues lower HbA1c more in Asian-dominant studies than in non-Asian-dominant studies. Further studies are warranted to explore the potential mechanisms of the ethnic difference.